Brother Can You Spare My Bladder? Neoadjuvant Chemotherapy and Bladder-Sparing
Brother Can You Spare My Bladder? Neoadjuvant Chemotherapy and Bladder-Sparing Surgery for Invasive Bladder Cancer
ABSTRACT & COMMENTARY
Standard therapy for invasive bladder cancer is radical cystectomy. However, in light of the influence of that operation on quality of life, selected patients are being managed with radiation therapy and/or chemotherapy followed by bladder-sparing surgical procedures.1-4 To date, no randomized studies have demonstrated that radical surgery and combined modality bladder-sparing approaches have comparable survival. However, pilot studies are defining a patient population in which bladder sparing might well be considered.
Herr and colleagues from Memorial Sloan-Kettering reported 10-year follow-up on a group of patients in whom neoadjuvant therapy was delivered for muscle-invasive bladder cancer and whose tumors appeared to respond completely to the chemotherapy (i.e., became T0). Between 1985 and 1989, 111 consecutive patients with T2-3N0M0 bladder cancer received MVAC chemotherapy (methotrexate 30 mg/m2 days 1, 15, and 22; vinblastine 3 mg/m2 days 2, 15, and 22; doxorubicin 30 mg/m2 day 2; cisplatin 70 mg/m2 day 2; cycles q28 days) as their first treatment and 60 of these (54%) became T0 as assessed by a negative biopsy of the tumor site and negative urine cytology after the fourth chemotherapy cycle. All of these patients were advised to have either a radical cystectomy or, if feasible, a partial cystectomy to document the response to MVAC or to remove residual invasive tumor not detected on transurethral resection.
Twenty-eight patients refused both surgical procedures; 15 had a partial cystectomy; 17 had radical cystectomy. Radiation therapy was not given to any of these patients. Of the 17 patients who had radical cystectomy after neoadjuvant chemotherapy, 11 (65%) are alive and free of disease. Of the 43 patients who retained all or part of their bladders, 32 (74%) are alive and 25 (58%) have a functioning bladder. Twenty-four patients (56%) developed recurrent bladder tumors five months to 8 years after treatment (median 41 months); these were invasive in 13 patients (30%) and superficial in 11 (26%). Patients with superficial relapse were all rescued with BCG (bacille de Calmette-Guerin) therapy. Of the 13 with invasive relapses, seven were salvaged with cystectomy and six died. Four of these six died from metastases that derived from their second malignant bladder tumor after a disease-free interval of more than two years. Three patients relapsed with transitional cell carcinomas occuring in urothelium outside of the bladder in the upper collecting system. (Herr HW, et al. J Clin Oncol 1998;16:1298-1301.)
COMMENTARY
These data present a good news/bad news picture. The good news, however, is really good. First, more than 50% of patients with invasive bladder tumors can have those tumors eradicated clinically with four cycles of MVAC chemotherapy, and more than 60% of those individuals (17 of 28 in this series) get to keep their bladders. This is somewhat surprising because these patients are staged with the cystoscope, and prior reports suggested that up to one-third of patients who were T0 by cystoscopy had residual invasive tumor in the resected bladder.5 However, other studies have found that cystoscopy misses few or no residual invasive tumors (this study found 1 tumor among 15 patients who underwent partial cystectomy, and Housset and colleagues found none among 18 cystectomy specimens).6 Thus, cystoscopy staging seems to be adequate to evaluate the response to neoadjuvant chemotherapy, and those who achieve an apparent complete response are likely not to lose their bladders.
However, the bad news is that the transitional epithelium is still under the influence of the field effect that generated the first malignancy. Four of the 43 patients who had bladder-sparing approaches to their management died when they developed second bladder cancers that then metastasized. It seems likely that the deaths of these patients, accounting for 9% of those whose bladders were spared, might have been prevented had they undergone cystectomy following the neoadjuvant chemotherapy. It is not clear whether the addition of radiation therapy to the treatment regimen would have further reduced the recurrence rate. The bottom line is that patients who wish to keep their bladders have to live with the persistent risk that new tumors will develop in their urothelium and that sometimes these tumors are outside the bladder. Thirty percent of patients who take a bladder-sparing approach ultimately require cystectomy for either recurrence or the development of a new tumor. Is the risk worth taking? Single-arm studies suggest that overall survival is not adversely affected; however, that projection has not been confirmed by randomized studies. Experience teaches us that some patients will be happy to accept the observed risk of recurrent or new disease to keep their bladders and others will prefer to have the bladder removed, putting the risk of local recurrence behind them.
References
1. Kaufman DS, et al. N Engl J Med 1993;329:1377-1382.
2. Herr HW, Scher HI. J Clin Oncol 1994;12:975-980.
3. Kachnic LA, et al. J Clin Oncol 1997;15:1022-1029.
4. Sternberg CN, et al. Urol Oncol 1995;1:127-133.
5. Splinter T, Denis L. Semin Oncol 1990;17:606-612.
6. Housset M, et al. J Clin Oncol 1993;11:2150-2157.
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